rs222780

Positions:

• chr17-3616353-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013276.4(SHPK):​c.824-816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,186 control chromosomes in the GnomAD database, including 756 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.088 (756 hom., cov: 31)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

Genes affected

SHPK (HGNC:1492): (sedoheptulokinase) The protein encoded by this gene has weak homology to several carbohydrate kinases, a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane. Sequence variation between this novel gene and known carbohydrate kinases suggests the possibility of a different substrate, cofactor or changes in kinetic properties distinguishing it from other carbohydrate kinases. The gene resides in a region commonly deleted in cystinosis patients, suggesting a role as a modifier for the cystinosis phenotype. The genomic region is also rich in Alu repetitive sequences, frequently involved in chromosomal rearrangements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHPK	NM_013276.4	c.824-816C>T		intron_variant		ENST00000225519.5	NP_037408.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHPK	ENST00000225519.5	c.824-816C>T		intron_variant		1	NM_013276.4	ENSP00000225519	P1

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13425 AN: 152068 Hom.: 751 Cov.: 31

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.0865

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0883 AC: 13445 AN: 152186 Hom.: 756 Cov.: 31 AF XY: 0.0908 AC XY: 6757 AN XY: 74398

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0910

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0859 Hom.: 71

Bravo AF: 0.0861

Asia WGS AF: 0.283 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs222780; hg19: chr17-3519647; COSMIC: COSV56648515; COSMIC: COSV56648515;